{"doi":"10.1016/j.dcn.2025.101624","title":"Brain functional connectivity, but not neuroanatomy, captures the interrelationship between sex and gender in preadolescents","abstract":"Understanding sex differences in the adolescent brain is crucial, as they relate to sex-specific neurological and psychiatric conditions. Predicting sex from adolescent brain data may reveal how these differences influence neurodevelopment. Recently, attention has shifted toward socially-identified gender (distinct from sex assigned at birth) recognizing its explanatory power. This study evaluates whether resting-state functional connectivity (rsFC), cortical thickness, or cortical volume better predicts sex and sex/gender alignment (congruence between sex and gender) in preadolescents. Using Adolescent Brain Cognitive Development (ABCD) Study data and machine learning, rsFC predicted sex more accurately (85%) than cortical thickness (76%) and cortical volume (70%). Brain regions most predictive of sex belonged to association (default mode, dorsal attention, parietal memory) and visual networks. The rsFC classifier trained on sex/gender aligned youth classified more accurately unseen youth with sex/gender alignment ( n = 2,013) than unalignment ( n = 1,116). The female rsFC sex profile was positively associated with sex/gender alignment, while in males, there was a negative association. However, neither brain modality predicted sex/gender alignment. These findings suggest that while rsFC predicts sex in the adolescent brain more accurately, it does not directly capture sex/gender alignment, underscoring the need for further investigation into the neural underpinnings of gender. • Resting-state functional connectivity (rsFC) predicts sex with an accuracy of 85%, significantly outperforming cortical thickness and cortical volume, which achieve 76% and 70% respectively. • Key brain networks involved in predicting sex include association networks (default mode, dorsal attention, and parietal memory) and visual networks (visual and medial visual). • The rsFC sex classifier trained on sex/gender aligned youth was significantly more effective in classifying individuals with sex/gender alignment compared to individuals with sex/gender unalignment. • In females, the degree to which their brains’ rsFC matched a sex profile (female or male), was positively associated with the degree of sex/gender alignment. • rsFC, cortical thickness, and cortical volume did not predict sex/gender alignment, emphasizing the complexity of the relationship between sex, gender, and brain functional connectivity and neuroanatomy.","journal":"Developmental Cognitive Neuroscience","year":2025,"id":547429,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":409763,"name":"Roselyne J. 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Baden","orcid":null,"position":10,"is_corresponding":false},{"id":986917,"name":"Vahdeta Suljic","orcid":null,"position":11,"is_corresponding":false},{"id":248174,"name":"Kristen M. Scheidter","orcid":null,"position":12,"is_corresponding":false},{"id":985068,"name":"Julia Monk","orcid":null,"position":13,"is_corresponding":false},{"id":1168312,"name":"Forrest I. Whiting","orcid":null,"position":14,"is_corresponding":false},{"id":1168311,"name":"Nadeshka Ramirez-Perez","orcid":null,"position":15,"is_corresponding":false},{"id":232787,"name":"Deanna M. Barch","orcid":"0000-0003-1693-8506","position":16,"is_corresponding":false},{"id":236740,"name":"Aristeidis Sotiras","orcid":"0000-0003-0795-8820","position":17,"is_corresponding":false},{"id":244883,"name":"Nico U.F. 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